Low doses of doxepin can be used to treat sleep disorders, such as insomnia. Sleep is essential for health and quality of life. Insomnia is a growing health problem in the United States. It is believed that more than 10-15 million people suffer from chronic insomnia and up to an additional 70 million people suffer from some form of insomnia each year. Insomnia is a condition characterized by difficulty falling asleep (sleep onset), waking frequently during the night (fragmented sleep), waking too early (premature final awakening), and/or waking up feeling un-refreshed. In the National Sleep Foundation's (NSF) Sleep in America Poll 2005, 42% of survey respondents reported that they awoke frequently during the night, 22% of adults reported waking too early and not being able to return to sleep and 38% reported waking and feeling un-refreshed.
Doxepin is a tricyclic compound currently approved for treatment of depression or anxiety at a daily dose of 75 mg to 300 mg. Non-liquid forms of doxepin are currently available in 10, 25, 50, 75, 100 and 150 mg capsules. Liquid concentrate doxepin is available in a dosage of 10 mg/mL. It should be noted that some embodiments can specifically exclude formulations of doxepin in capsule form, in particular capsules with a powder therein. Capsules with 10 or more mg of doxepin can be excluded from some embodiments. Also, gelatin coated capsules with or without a powder therein can be excluded from some embodiments. Methods of treating sleep using 10 mg capsules or drug taken (e.g., taking a fraction of the powder from the capsule) or derived (e.g., diluting material from a capsule prior to taking) from 10 mg capsules can be specifically excluded from some embodiments.
Making low dose formulations can present technical and economic challenges that are not present for higher dose formulations. Furthermore, existing doxepin formulations do not take into account the unique aspects of sleep disorders.
Embodiments of the invention provide low dose formulations of doxepin and doxepin compounds, and also address and overcome the challenges and problems associated with formulating and manufacturing low-dose doxepin dosage forms.